Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists as Adjuncts to Insulin Therapy in Type 1 Diabetes Mellitus: An Overlap-Informed Umbrella Review
- Design
- Umbrella review · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Population unclear[Auto] Synthesis; population mix not determinable from abstract. Review the included-study populations.
- Could weight loss explain it?
- Unknown[Auto] Not addressed in abstract.
- Study tier
- Study tier 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; quoted from abstract conclusions] Adjunctive GLP-1RA therapy was associated with a modest reduction in HbA1c and clinically relevant reductions in body weight and insulin requirements, without a significant improvement in time in range. Gastrointestinal adverse events were increased, whereas the risks of diabetic ketoacidosis and severe hypoglycemia remained uncertain. These findings do not support routine use but suggest a potential role in selected individuals for whom weight reduction and lower insulin requirements are therapeutic priorities.
01Findings
What the study reported
- Drugs
- Class unspecified
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Diabetes status
- type 1 diabetes
Study quality details
- Study design
- Umbrella review
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- intermediate
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- UNKNOWN
- Statistical precision
- CI reported: 95% confidence intervals (CIs
- Risk of bias
- not assessed (auto)
- Funding conflicts
- no
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Ministry of Health and Welfare; Ministry of Science and ICT, South Korea; Soonchunhyang University Research Fund
- Industry funded
- No
- Manufacturer
- None identified
- Sponsor role
- no manufacturer funding identified
- Author conflicts
- not available in metadata
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[AIM] Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potential adjuncts to insulin therapy for type 1 diabetes mellitus (T1DM). However, interpretation of the available evidence is complicated by substantial primary-study overlap, methodological heterogeneity and variable certainty of evidence. Thus, we conducted an overlap-informed umbrella review to evaluate the efficacy and safety of GLP-1RAs as adjunctive therapy in T1DM. [MATERIALS AND METHODS] We searched PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and OpenAlex from inception to 22 June 2026, and manually screened reference lists to identify systematic reviews with meta-analyses that included randomized controlled trials (RCTs), either alone or alongside nonrandomized studies, evaluating adjunctive GLP-1RA therapy in T1DM. Methodological quality was assessed using AMSTAR 2, and primary-study overlap was quantified using a citation matrix and corrected covered area (CCA). Outcome-specific representative meta-analyses were selected, and their primary-study data were independently reanalyzed using random-effects models. Continuous and dichotomous outcomes were summarized as mean differences (MDs) and risk ratios (RRs), respectively, with 95% confidence intervals (CIs). The certainty of evidence was assessed using GRADE. [RESULTS] Eighteen systematic reviews with meta-analyses encompassing 56 unique primary studies (35 RCTs and 21 nonrandomized studies) were included. The calculated CCA was 19.6%, indicating a very high degree of primary-study overlap, largely driven by the ADJUNCT ONE and ADJUNCT TWO trials. Adjunctive GLP-1RA therapy reduced HbA1c (MD, -0.23% [95% CI, -0.30 to -0.17]; moderate certainty), body weight (MD, -3.93 kg [-4.29 to -3.56]; moderate certainty) and total daily insulin dose (MD, -5.74 IU/day [-7.30 to -4.17]; low certainty). No significant improvement was observed in time in range (MD, 1.99% [95% CI, -1.17 to 5.15]; very low certainty). No statistically significant increases were observed in severe hypoglycemia (RR, 0.83 [95% CI, 0.36-1.91]; low certainty) or diabetic ketoacidosis (RR, 0.67 [95% CI, 0.16-2.86]; low certainty). However, GLP-1RAs increased the risks of nausea (RR, 2.88 [95% CI, 2.20-3.76]; high certainty), vomiting (RR, 3.11 [1.94-4.97]; high certainty), and withdrawal due to adverse events (RR, 2.10 [1.42-3.12]; high certainty), whereas the risk of diarrhoea was not significantly increased (RR, 1.88 [0.82-4.33]; low certainty). [CONCLUSIONS] Adjunctive GLP-1RA therapy was associated with a modest reduction in HbA1c and clinically relevant reductions in body weight and insulin requirements, without a significant improvement in time in range. Gastrointestinal adverse events were increased, whereas the risks of diabetic ketoacidosis and severe hypoglycemia remained uncertain. These findings do not support routine use but suggest a potential role in selected individuals for whom weight reduction and lower insulin requirements are therapeutic priorities.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 42723273 first ingestion |